Using a whole genome scan, we will assess genetic linkage to alcoholism and associated psychiatric disorders in Choctaw American Indians. Choctaw is a large Eastern North American Indian tribe with over 30,000 enrolled members living within tribal boundaries in Oklahoma. By contrast to neighboring American Indian tribes that have high prevalences of alcoholism, this tribe stands out because alcoholism has a low prevalence, about 1% and 10% of females and males, respectively. By studying American Indians in the context of low alcoholism, we can expect to reveal differences in the roles of genetic and/or environmental determinants of alcoholism. Genetic analysis is to be conducted using two samples from the tribe: a small random sample (N=100) and large extended families (N=200 tested subjects). The sampling design accommodates case-control association analyses and non-parametric two- and multi-point linkage methods. In order to perform the analyses outlined above, individual psychiatric interviews and blood samples have been collected. Research diagnoses are made from the psychiatric interviews and DNA for genotyping is being extracted from the blood samples. For the linkage analysis, we expect to type up to 2000 unique sequence DNA polymorphisms spanning the entire human genome as the technology becomes available. Database checks and epidemiological analyses are now under way and we are assessing the reliability of psychiatric diagnoses made using different systems, e.g. DSM-III-R, DSM-IV and ICD 10. We are also examining individual differences in cultural experience and how they relate to vulnerability to alcohol related problems.